Advanced healthcare materialsOct 23, 2024

Increasing Protein Production from Introduced mRNA Using Moving Mechanical Forces

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 29, 2026

Abstract

Mechanical oscillation at 65 Hz enhances endosomal escape of mRNA delivered by lipid nanoparticles.

Mechanical oscillation prompts lipid nanoparticles to fuse with one another, improving endosomal escape.
Endosomal escape of mRNA is significantly enhanced, leading to increased transfection efficiency.
Cell viability remains high at 99.3% following treatment with oscillation, similar to untreated cells.
No significant damage is observed to mitochondrial membrane potential or the integrity of the Golgi apparatus.
This approach may provide a safe and effective method for improving nucleic acid delivery in research and clinical applications.

Simplified

Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.

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Increasing Protein Production from Introduced mRNA Using Moving Mechanical Forces

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